缺氧诱导因子脯胺酸羟化酶
| Hypoxia-inducible factor-proline dioxygenase | |||||||
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| 识别码 | |||||||
| EC编号 | 1.14.11.29 | ||||||
| 数据库 | |||||||
| IntEnz | IntEnz浏览 | ||||||
| BRENDA | BRENDA入口 | ||||||
| ExPASy | NiceZyme浏览 | ||||||
| KEGG | KEGG入口 | ||||||
| MetaCyc | 代谢路径 | ||||||
| PRIAM | 概述 | ||||||
| PDB | RCSB PDB PDBj PDBe PDBsum | ||||||
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HIF脯胺酸羟化酶（英语：HIF prolyl-hydroxylase）是一个包含在缺氧诱导因子（英语：Hypoxia-inducible factor，简称：HIF）讯息路径中的酶，也是一系列称为HIF脯胺酸羟化酶抑制剂 治疗性药物的目标
缺氧诱导因子(HIF)是一个在演化上被保留下来的转录因子[1]，它让细胞可以针对低氧浓度环境作出生理性的反应[2]。其中一种特定作用在HIF上的脯胺酸羟化酶已经被确认存在；[3]而羟基化的HIF能让蛋白质被作为降解的目标[3]
HIF脯胺酸羟化酶已经被各式各样抑制剂作为目标，用来治疗中风[4]，肾脏疾病[5]缺血[6]，贫血[7]，和其他重大疾病。在红血球过多症相关以及乳癌相关的PHD2突变的案例中，临床观察下的脯胺酸羟化酶区域突变会影响它对HIF受质的选择性，这点对药物设计有重要的意义[8] 。 在人体中，HIF脯胺酸双氧化酶有三种种型。分别是 PHD1、PHD2和PHD3。其中，PHD2因为它对氧气缓慢的反应速度而被视为人体最重要的氧气感应器[9]。
参考文献
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- ^ Warnecke, C.; Griethe, W.; Weidemann, A.; Jurgensen, J. S.; Willam, C.; Bachmann, S.; Ivashchenko, Y.; Wagner, I.; Frei, U. Activation of the hypoxia-inducible factor pathway and stimulation of angiogenesis by application of prolyl hydroxylase inhibitors. The FASEB Journal. 2003, 17 (9): 1186–8. PMID 12709400. doi:10.1096/fj.02-1062fje.
- ^ Selvaraju, V; Parinandi, N. L.; Adluri, R. S.; Goldman, J. W.; Hussain, N; Sanchez, J. A.; Maulik, N. Molecular Mechanisms of Action and Therapeutic Uses of Pharmacological Inhibitors of HIF-Prolyl 4-Hydroxylases for Treatment of Ischemic Diseases. Antioxidants & Redox Signaling. 2013, 20 (16): 2631–2665. PMC 4026215 . PMID 23992027. doi:10.1089/ars.2013.5186.
- ^ Muchnik, E; Kaplan, J. HIF prolyl hydroxylase inhibitors for anemia. Expert Opinion on Investigational Drugs. 2011, 20 (5): 645–56. PMID 21406036. doi:10.1517/13543784.2011.566861.
- ^ Chowdhury, Rasheduzzaman; Leung, Ivanhoe K. H.; Tian, Ya-Min; Abboud, Martine I.; Ge, Wei; Domene, Carmen; Cantrelle, François-Xavier; Landrieu, Isabelle; Hardy, Adam P. Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Nature Communications. 2016-08-26, 7: 12673. PMC 5007464 . PMID 27561929. doi:10.1038/ncomms12673 （英语）.
- ^ Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J. HIF prolylhydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia. EMBO J. Aug 2003, 22 (16): 4082–4090. PMC 175782 . PMID 12912907. doi:10.1093/emboj/cdg392.
